While the Man Full of Trouble Tavern isn't Philadelphia's most famous structure, it is one of the oldest. Like many of the city's earliest taverns, such as the Blue Anchor, the Penny Pot Tavern and Landing, and the Indian Queen Hotel, Man Full of Trouble, built in 1759, was near the Delaware River, and it still stands at its original location at 127 Spruce St.

Unlike the City Tavern and the London Coffee House that attracted the city's wealthier residents, the Man Full of Trouble offered beer, cider, and rooms to the down-to-earth waterfront crowd of workers and residents. The building consists of three floors - the barroom was on the first, the rooms (or mattresses) for rent were on the second, and the kitchen and hired workers resided in the cellar.

The tavern was built by Michael Sisk and frequently changed hands until 1796, when widow Martha Smallwood began her 30-year administration. At the end of the 18th century, nearly a fifth of the taverns and coffeehouses in Philadelphia were managed by women, as tavern licenses were often restricted to widows. Over the next century and a half, the structure survived as a watering hole, a hotel, and a chicken market.

In the 1960s, Councilwoman Virginia Knauer bought the Man Full of Trouble and a neighboring building to restore them, and she invited students from the University of Pennsylvania to conduct an archaeological survey of the site. In 1994, the building became the property of Penn, which manages the site, though the grounds are looked after by private individuals.